A Brief history of Immunology

We live in a dangerous world full of a billion pathogens ready to infect us at any time. No wonder nature has endowed us with a strong immunity against these pathogen.

The whole history of our knowledge about such an important life story is hardly 120 years. The first Nobel prize in medicine was awarded in 1901 for Anti Diphtheritic serum. At that time we did not know that it is a solution of humoral immunity or antibodies. Subsequently the Y shaped immunoglobulins with its Fc binding and Ag binding components are discovered. The role of anti serum in protecting against pathogen was show great that even after 120 years in 2020 when Covid 19 happened and we didn’t have a definitive drug against it , we started using Plasma therapy with little or no advantage.

we are now sure that factors other than simple antibodies matter in the long term protection against intracellular pathogens like viruses. Antibodies circulate in blood and are very competent in neutralising circulating pathogens. When the pathogen lurks inside a cell, they need the help of various cells like killer cells, NK cells to destroy the affected cells.

Exactly half way, around the 1960s, thaat is 60 years after the antibodies, we recognised Cell Mediated Immunity. It was mainly in the domain of Transplant genomics like Graft versus Host (GVH) reactions. In 1980s during the AIDS pandemic we counted the CD4 cells in the blood of serious patients regularly. The role of T Helper cells (TH) and T Suppressor cells were delineated.

But the field of immunology was revolutionised in 2011, when the Nobel prize in medicine was awarded to Innate immunity as the gate keeper of our immunity against all type of infection. Ralph Steinman had already discovered the Dendritic cells in 1973, 40 years ago. Butler and Hoffman discovered the role of Toll Like Receptors (TLR) in activating Innate immunity.

Now we know that whenever a foreign organism be it a virus or bacteria, the first line of our defence are these Dendritic cells. They can destroy the viruses and we shall have no knowledge that a threat has been neutralised. 99% of viral invasions are taken care of by our innate immunity. Some times they unleash a slew of inflammatory mediators leading to raised temperature, cytokines and we get the prodromal symptoms of viremia. But again 90% of viral infections are taken care of within the first week. Thus most of the viral common cold and Flus are cured within 7 days because of our innate immunity. its is a non specific immunity present in both mammals and no mammals since the beginning of evolution. Adaptive Immunity like antibodies and immune memory are added in primates only.

When the virus progresses beyond one week, they inform our adaptive immunity the complex system antibodies and T cells. And a immunological memory is kicked off.

The Enigmatic story of Ralph Steinman.

Our whole knowledge of immunology was revolutionised by the Nobel prize of 2011. After 111 years in the story of immunity, was added the chapter of Innate Immunity. since then all literature related to viral infections are incomplete without mention of any role of innate immunity.

Ralph Steinman had identified the Dendritic cells and their role in immunity in the 1973s. But the 70s were the heady days of antibodies and recombinant technology. It would take another decade for us, that is in 1980s when the AIDS pandemic struck, that we recognised the role of T cells as immune mediators. So the findings of Ralph Steinman were never taken seriously.

The nostalgic story on that 3rd October in 2011.

At 10.42 am of October 3, 2011 the Nobel committee announced Ralph Steinman as the winner of half of the award money of the Nobel Prize of the year.

At 2.42 pm, the committee were informed that Ralph Steinman had died just 3 days before the awards and a stalemate arose. Nobel Prize statutes do not allow it to be awarded posthumously. Otherwise, Mahatma Gandhi would have been a strong contender for such a posthumous Peace Nobel.

It took 4 hours to Nobel committee to break the tradition.

At 4.44 pm that same day, the president of the Royal Society and Nobel laureate, Sir Paul Nurse, writes:

“This is a great tragedy. Ralph Steinman‘s work was ahead of its time and he waited too long for the Nobel prize. To die just days before its announcement is almost too much to bear. He will be remembered as one of the great immunologists of our time.”
Nobel committee

So on 4th October, Tuesday the Committee concluded that the 2011 Nobel Prize in Medicine will be awarded to Ralph Steinman posthumously.

And the field of immunology completed changed.

For example the BioNTech people Dr Ugur Sahin and madam Tureci always counted the number of T cells that are sensitised post vaccination in their laboratory in German.

The Genome sequence of the Covid19 virus was available in public domain in January of 2020. Both Moderna and BioNTech were ready with prototype vaccines within 45 days, by February end. The phased Clinical Trials took a total 6-7 months and after Billions of dollars pumped in by the manufacturers, a vaccine was injected to shoulders of only on December 8,2020. Below is the twitter image dated 11 January, 20202 telling the whole world about the genome sequence of the Covid virus.

It took 10 months.

At University Hospital, Coventry, matron May Parsons administered the very first injection to the 91 years old Margaret Keenan and the historic syringe was whisked away to be kept in museum along with Edward Jenners syringe for the posterity.

Moderna was confident in their in-house technology, and are funded by the US Government. But BioNTech didn’t have the funds and means to conduct the gigantic Clinical trials required before authorisation of vaccines. So they have to take the help of the Pharma giant Pfizer to do the needful.

Now here is a question for you ? In the early 2020s, BioNTech was an unknown entity. What convinced the Pfizer people to invest 7 billion dollars on a totally untested technology (mRNA product) form a virtual unknown entity in the field of vaccines.

Dr Ugur Sahin and Ozlem Tureci showed them their realistic lab data of T cell immunity against the covid virus conducted in their make shift lab in the forests of Marburg.